Connexins 26 and 32 in the developing neocortex

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During neocortical neurogenesis, the basic structure of the neocortex arises through a precise coordination of cell division, specification, migration, and circuit formation. These processes are influenced, if not defined, by cell-cell interactions. Gap junctions---transmembrane proteins that allow direct electrical or biochemical communication between cells---are a prevalent and important mode of cell-cell signaling throughout neocortical development. Gap junction channels are composed of 12 connexin subunits and may display different signaling properties depending on which connexins are present. We investigated the expression of two connexin subunits, Cx26 and Cx32, during neocortical neurogenesis in the mouse, a period spanning embryonic days 12 and 17 (E12--E17). The purpose of our initial study was to elucidate possible developmental roles for Cx26 and Cx32 by comparing their expression patterns in populations of cells undergoing distinct developmental events: proliferation, migration, or differentiation. We found that Cx26 and Cx32 are both expressed throughout neocortical neurogenesis in all three populations of cells. This spatial and temporal overlap in expression suggests the possible formation of Cx26/Cx32 heteromeric channels, a well described channel configuration with distinct properties. However, through most of neurogenesis, Cx26 shows significant variation in expression between proliferating, migrating, and differentiating cells while Cx32 expression remains relatively uniform. In our second study, we addressed more directly the possible developmental role for Cx32 by examining the neocortex of Cx32 null embryos at E17, the culmination of neurogenesis. We analyzed the embryos using a series of established histological and immunological markers of neocortical development and found no apparent disruption of normal neocortical development in the absence of Cx32. We did, however, find evidence for an upregulation of Cx26 expression in Cx32 null neocortex. This result, in addition to suggesting a possible mechanism for compensation, attests to the importance of gap junctional communication to normal neocortical development. In a third study, we discovered and isolated DECORE, a cortex specific protein that may be involved in the development of distinct neocortical layers.